Massive expansion of a DNA hexanucleotide sequence repeat (C2G4) within the human C9orf72 gene has been linked to a number of neurodegenerative diseases. In sodium or potassium salt solutions, single-stranded d(C2G4)n DNAs fold to form G-quadruplexes. We have found that in magnesium or lithium salt solutions, especially under slightly acidic conditions, d(C2G4)n oligonucleotides fold to form a distinctive higher order structure whose most striking feature is an “inverted” circular dichroism spectrum, which is distinguishable from the spectrum of the left handed DNA double-helix, Z-DNA. On the basis of CD spectroscopy, gel mobility as well as chemical protection analysis, we propose that this structure, which we call “iCD-DNA”, may be a left-handed Hoogsteen base-paired duplex, an unorthodox G-quadruplex/i-motif composite, or a non-canonical, “braided” DNA triplex. Given that iCD-DNA forms under slightly acidic solution conditions, we do not know at this point in time whether or not it forms within living cells.

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(C2G4)n repeat expansion sequences from the C9orf72 gene form an unusual DNA higher-order structure in the pH range of 5-6

Sixty-four sets of three-dimensional models of DNA triplex base triplets (TBT) were built up based on codons by homologous modeling method and their energies were minimized. According to sequence of TBT and orientation of the third ODN strand third, the energies of monomers and water-K+-TBT ternary complexes of TBT were analyzed. The results showed: (i) The energies of the symmetric parallel monomers are generally lower than those of the symmetric anti-parallel monomers of TBT, but the energies of the symmetric parallel ternary complexes are higher than those of the symmetric anti-parallel ternary complexes of TBT. (ii) No matter TBTs are monomers or ternary complexes, the energies of asymmetric parallel TBTs are generally lower than those of the asymmetric anti-parallel ones. (iii) Although the energies of the parallel TBTs are correlated with those of the anti-parallel ones, the energy differences are significant between them. The results here suggest the sequences of TBTs and the orientations of the third ODN strands are two of the key factors that can influence the formation and stability of TBT. (C) 2002 Elsevier Science B.V. All rights reserved.

J.-S. Zhao

Papers

A Molecular Model of Braid-like DNA Structure

Syntheses, Structures, Luminescence Properties of Two Coordination Polymers Constructed by a Semirigid Aromatic Multicarboxylite Ligand